Project Abstract Many psychiatric disorders including schizophrenia, depression, and autism, are associated with disrupted sleep. Disrupted sleep may contribute to negative cognitive symptoms, as sleep is crucial for maintaining and restoring healthy brain function. In particular, the slow (0.1-1 Hz) oscillations characteristic of deep sleep are thought to play essential roles in the restorative functions of sleep, and these oscillations have complex spatial properties that may be important for their effects on cognition. However, determining how slow oscillations influence brain function has been challenging due to our current inability to measure slow oscillations with spatial precision throughout the whole brain. This project exploits the recent development of accelerated multi-slice imaging methods to measure fast (>0.2 Hz) fMRI signals. This work is centered around an innovative use of accelerated fMRI with simultaneous EEG to directly measure slow oscillation dynamics throughout the human brain simultaneously, and use this information to create the first whole-brain maps of slow oscillations. We will first optimize imaging and analysis methods for localizing slow oscillations. We will then test a hypothesis for how slow oscillations affect cognitive function: namely, that spatially localized slow oscillations in cortex and thalamus lead to reorganized information transfer across cortical networks, and thereby influence cognitive function. The candidate has expertise in systems neuroscience of arousal regulation, anesthesia pharmacology, electrophysiology, and signal processing, providing a strong foundation for conducting this advanced imaging study of sleep states. The K99 will provide necessary training in 1) functional and anatomical MRI; 2) simultaneous EEG-fMRI during sleep; and 3) human sleep neurophysiology. The research will take place at the Athinoula A. Martinos Center, a highly collaborative environment equipped with state-of-the-art facilities for neuroimaging. The primary mentor Prof. Bruce Rosen will provide mentorship in neuroimaging and in transitioning to an independent position. In addition, the co-mentor Prof. Robert Stickgold will provide training in sleep neurophysiology, as well as exposure to clinical contexts of how sleep is affected in psychiatric disorders, and how disrupted sleep can contribute to cognitive deficits. Additional advice from Dr. Jonathan Polimeni and Dr. Jeff Duyn on imaging and analysis techniques will ensure high-level training in these methodological approaches. This methodological and scientific training will enable the candidate both to successfully complete these aims and to develop an independent research program focused on the systems neuroscience of sleep and arousal regulation, how sleep circuits and sleep-modulating pharmaceutical agents influence cortical function, and how sleep deficits lead to disrupted cognition. The results of this research will contribute to improved methods for imaging dynamics in the human brain, and shed light on the effects of sleep deprivation, which have significant negative effects both on the general population and particularly in patients with psychiatric disorders.